Functionally modified gelatin microspheres impregnated collagen scaffold as novel wound dressing to attenuate the proteases and bacterial growth.
An attempt was made to develop a new therapeutic delivery system which would play a dual role of attenuating MMP activity in the wounds and also prevent infection by controlled delivery of antimicrobials. A catechol type MMP inhibitor 2,3-dihydroxybenzoic acid (DHBA) was conjugated to gelatin microspheres using EDC/NHS as coupling agents. The potential of the modified gelatin microspheres (DHB-MS) to attenuate the proteases such as MMP 2 and MMP 9 in the diabetic wound tissues was investigated by gelatin zymography. Further the modified microspheres were loaded with doxycycline and impregnated in a reconstituted collagen scaffold as novel wound dressing. The in vitro release behavior of doxycycline from both DHB-MS and DHB-MS impregnated collagen scaffold was investigated. DHB-MS when incubated with the tissue lysate for 6h displayed the complete inhibition of the MMPs in the tissue lysate. The in vitro drug release studies from the collagen scaffold exhibited the burst release of 44%, exerted immediate chemo prophylaxis and sustained delivery for 72 h. The MTT assay and fluorescent labeling with calcein AM indicated that the DHB-MS is biocompatible to human foreskin fibroblasts. Thus the system developed provides wider scope to control the pathogens involved in infection and also the excess matrix degradation.
Adhirajan
N
N
Biomaterials Division, Central Leather Research Institute, TICEL Biopark, Tharamani Road, Tharamani, Chennai 600113, Tamil Nadu, India.
Shanmugasundaram
N
N
Shanmuganathan
S
S
Babu
Mary
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001458:Bandages; D001682:Biological Availability; D002396:Catechols / Q000008:administration & dosage / Q000737:chemistry; D002417:Cattle; D002470:Cell Survival; D003094:Collagen / Q000737:chemistry*; D004318:Doxycycline / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D005296:Ferrous Compounds / Q000737:chemistry; D005347:Fibroblasts / Q000166:cytology; D016523:Foot Ulcer / Q000201:enzymology; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D062385:Hydroxybenzoates; D008422:Materials Testing; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D014867:Water / Q000737:chemistry; D014945:Wound Healing
D000900:Anti-Bacterial Agents; D002396:Catechols; D005296:Ferrous Compounds; D062385:Hydroxybenzoates; D011480:Protease Inhibitors; D014867:Water; C020748:ferrous sulfate; C009135:2,3-dihydroxybenzoic acid; D005780:Gelatin; D003094:Collagen; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline